Mycobacterium tuberculosis is the commonest pathogen leading to fatal opportunistic disease in sub-Saharan Africa. This proposal aims at demonstrating the benefits of antiretroviral therapy on TB in the community of Masiphumelele. Because the major cause of morbidity and mortality in HIV-1 infected adults and children is TB, safeguarding the household from the disease is a public health priority Countries in Africa are experiencing rapid increases in tuberculosis (TB), and other respiratory diseases, which is attributable to an explosive HIV-1 epidemic, ineffective TB control programs and difficulties in the accurate diagnosis and management of infections o). HIV-1 fuels the TB epidemic in two ways: 1) HIV-1 is the most powerful risk factor for reactivation of latent TB infection to active disease, and 2) HIV-1 infected persons who become newly infected or re-infected with Mycobacterium tuberculosis progress much more rapidly to active TB. This study is of crucial importance because: South Africa is one of 5 countries with HIV-positive TB >300 cases/100,0000) There are 1600 new HIV infections daily in South Africa, 3.6 million already infected. TB control programs including DOTS have not been able to contain incident active TB. The increase of TB in HIV negative individuals relates to the increasing HIV (2). Tuberculosis consumes resources and shifts them from the HIV uninfected population. Introduction of ART may be more feasible if we demonstrate an impact of ART on TB incidence. Our group is uniquely qualified to conduct this research because: Dr Linda-Gaii Bekker has a long standing record of clinical, epidemiological and basic science research, of tuberculosis. (3.4) We have a well established TB program based on the WHO guidelines including DOTS, managed at a primary health care level, with tuberculosis reference labs, and diagnostic laboratory resources [unreadable]). Our Masiphumelele site has an effective notification and surveillance system We have established international research links with TB and HIV researchers: Prof. Gilla Kaplan, (Rockefeller university), Prof. Barry Kreiswirth( Public Health Research Laboratory, NY, who will provide the training and support required by this project to transfer the RFLP technology to Cape Town. John McKinney (Rockefeller University) Prof. Alan Aderem (Institute of Systems Biology, Seattle) Prof. Michael Tovey (Pasteur Institute, Paris)